Diastereo- and Enantioselective Synthesis ofN-Protected 2-Amino 1,4-Diols by an Oxa Michael Addition/1,3-Dipolar Cycloaddition Protocol

Abstract

An enantioselective synthesis of N-protected amino diols has been accomplished by employing a diastereoselective inter- and intramolecular 1,3-dipolar cycloaddition reaction of optically active nitrile oxides as a key step. The nitro alkane starting materials were obtained by diastereoselective oxa Michael addition of (1R,2S)-(–)-N-formylnorephedrine (1) to aliphatic (E)-nitro alkenes 2, 6a, b (de = 96 – ≥ 98%). Subsequent diastereo- and regioselective cycloaddition reactions to highly substituted 4,5-isoxazolines 5a–e, 8a, b (52-81%) and reductive ring opening led – after cleavage of the auxiliary – to amino diols 13, 14 in good overall yields (27-40%, over five steps) and with excellent diastereomeric and enantiomeric excesses (de,ee ≥ 96%).